RECEPTIVE MECHANISMS OF EXCITATORY AMINO-ACID SIGNALS

Excitatory amino acid (EAA) receptors are nowadays divided into 2 major categories according to their signal transduction systems. A metabotropic type of EAA receptors is linked to hydrolysis of peculiar phospholipids or formation of cyclic nucleotides, while an ionotropic type is associated with an ion channel permeable to particular cations. The ionotropic receptors are further classified on the basis of differential sensitivity to excitement by the exogenous agonist N-methyl-D-aspartic acid (NMDA). Ionotropic receptors insensitive to NMDA are distinguishable by preference to excitation by the other exogenous agonist alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic or kainic acid. These ionotropic receptors have been analyzed by conventional ligand binding techniques which often meet with critical methodological pitfalls and artifacts. In this review, therefore, our data obtained using accurate and reproducible receptor binding and gel-shift assays will be outlined with respect to signal transduction mediated by EAA from cell membranes to nuclei. Pharmacological evaluation is also discussed on the search for and the development of drugs useful for therapy and treatment of a variety of neurodegenerative disorders associated with dysfunction of EAA receptors.